96% |
With 1,3-dibromo-5,5-dimethylhydantoin; sodium hydroxide In lithium hydroxide monohydrate at 25℃; for 36h; |
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94.2% |
With bromine In chloroform for 5h; Reflux; |
88 2-bromo-3,4,5Trimethoxybenzoic acid(Intermediate 233) Preparation:
3,4,5-trimethoxy-benzoic acid (2.12g, 10.0mmol) was dissolved in 100mL of chloroform was added bromine (1.0mL, 20.0mmol), the reaction was refluxed for 5h. The reaction was washed successively with saturated sodium thiosulfate solution, washed with water to separate the organic phase was evaporated to dryness, water and recrystallized from ethanol to give a white solid 2.74g, yield 94.2%. |
94.2% |
With bromine In chloroform for 5h; Reflux; |
7 Preparation of 2-bromo-3,4,5-trimethoxybenzoic acid (Intermediate 52):
Dissolve 3,4,5-trimethoxybenzoic acid (10.0 mmol) in 100 mL of chloroform, add bromine water (20.0 mmol) ), refluxed for 5h.The reaction solution was washed with saturated sodium thiosulfate solution and water in turn, the organic phase was separated and evaporated to dryness, and recrystallized from water and ethanol to obtain 2.74 g of white solid with a yield of 94.2% |
93% |
With NBS In acetonitrile at 0 - 2℃; for 16h; |
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91% |
With sodium hydroxide; 1,3-dibromo-5,5-dimethylhydantoin Ambient temperature; |
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87.9% |
With bromine In chloroform; lithium hydroxide monohydrate for 18h; Reflux; |
1 Embodiment 1 : 2, 3, 4-trihydroxy-acridine -9 (10H)-one (compound 1) preparation of
A solution of 21.2 g (0.1 mol) of 3,4,5-trimethoxybenzoic acid dissolved in 150 mL of chloroform and 10 mL of water was weighed and 5.13 mL (0.10 mol) of liquid bromine was added with stirring. The solution turned dark red, the reaction was refluxed for 18 h, and then cooled to room temperature. Washed three times, evaporated to dryness, and the residue was a pale yellow solid. Recrystallization from ethanol / water (200 mL / 300 mL) gave 25.6 g of 2-bromo-3,4,5-trimethoxybenzoic acid as white needles, in 87.9% yield, m.p. 144-145 ° C. |
83% |
With bromine In chloroform; lithium hydroxide monohydrate for 10.5h; Reflux; |
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80% |
With NBS In chloroform for 8h; Heating / reflux; |
1
N-Bromosuccinimide (NBS) (21.36 g, 120 mmol) was added to a solution of 3,4,5-trimethoxy benzoic acid (compound 1a) (21.22 g, 100 mmol) in CHCl3 (200 mL). This solution was heated under reflux for 8 hours. Then, the CHCl3 was removed under reduced pressure, and the residue was dissolved in a 1 N NaOH solution (150 mL). After washing with CHCl3 (15 mL) three times, this alkaline solution was acidified with concentrated hydrochloric acid. The resulting precipitates were filtered off, washed with 1 N HCl, and dried to give the title compound 2a (2-bromo-3,4,5-trimethoxybenzoic acid) (23.3 g, 80 mmol/ yield: 80%). The NMR spectrum of the obtained compound 2a is shown in Table 1. Table 1 NMR spectrum of compound 2a400 MHz 1H NMR (CDCl3) δ 7.40 (1H, s, Ar-H), 3.97 (3H, s, OCH3), 3.91 (3H, s, OCH3), 3.90 (3H, s, OCH3). |
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With chloroform; bromine |
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With chloroform; bromine; iron(0) |
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With bromine; glacial acetic acid |
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With bromine In chloroform; lithium hydroxide monohydrate |
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With bromine In glacial acetic acid |
8.a 2-Bromo-3,4,5-trimethoxybenzoic acid 5
2-Bromo-3,4,5-trimethoxybenzoic acid 5 A solution of bromine (100 mmol) in 100 mL of acetic acid is added dropwise to a solution of 3,4,5-trimethoxybenzoic acid (100 mmol) in 100 mL of acetic acid cooled by an ice water bath. After the red color of the resulting mixture is discharged, the mixture is poured onto 500 g of crushed ice. The resulting solid is collected by filtration, dried over P2O5 in vacuo, and recrystallized from Et2O to give the product as a pale yellow solid. |
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With bromine In chloroform Inert atmosphere; |
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With bromine In chloroform; lithium hydroxide monohydrate |
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